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New vaccinal strategy

a new vaccinal strategy and vaccine technology, applied in the field of new vaccinal strategies, can solve the problems of limited induction of effector t cells, disappointing clinical efficacy, and the inability to vaccinate with full-length recombinant proteins,

Pending Publication Date: 2021-05-27
INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM) +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a vaccine composition that targets melanoma or metastatic melanoma. The vaccine contains a specific antigen peptide that is processed and presented by antigen presenting cells. The vaccine is designed to enhance the patient's own immune response to the melanoma antigen. The vaccine administration involves the return of T cells that recognize the melanoma antigen into the patient's body, which can lead to the destruction of tumor cells and the treatment of tumor. The patent also describes a method for testing the efficiency of the vaccine composition using T cells.

Problems solved by technology

Minimal CTL epitope, usually 9-10 amino acids in length led to limited induction of effector T cells associated with disappointing clinical efficacy.
This anergy probably resulted from exogenous loading of the short epitope and direct presentation to CD8 T cells, thus bypassing intracellular processing of the antigen by DC and co-signaling by matured DC (3) On the other hand, vaccination with full length recombinant proteins does not seem to be the best alternative.
However, no rationale for designing optimal linker is already presented.

Method used

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Examples

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[0147]Material & Methods

[0148]Peptide Synthesis

[0149]Designed peptides were purchased at >90% purity (Protogenix, Genecust). Lyophilised powder was resuspended at 10 mMstock in DMSO and stored at −80° C. Purity was assessed by HPLC and precise quantification was calculated based on protein content analysis.

[0150]Mice

[0151]HLA-DRB1*0101 / HLA-A*0201 transgenic mice (A2 / DR1 mice) have been previously described (Pajot et al Eur. J. Immunol 2004, Dosset et al Clin Cancer Res, 2012, Rangan et al Oncotarget, 2017). Mice were bred and housed at Animalerie centrale UFC / UFR “SMP” Besançon. Female mice 6-10 weeks old were used in the experiments. All experiments were performed according to the good laboratory practices after agreement #58 by the local ethical committee.

[0152]Tumor Cell Line

[0153]The SARC-L1 cell line which spontaneously occurred in A2 / DR1 mice was genetically modified to over-express HLA-A*0201 as previously described (Rangan et al Oncotarget, 2017). SARC-A2 cells were then tra...

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Abstract

The present invention relates to the prevention and treatment of disease like cancer. The inventors have previously characterized MELOE-1 antigen as an IRES dependent, melanoma specific translation product from a lncRNA mainly transcribed in the melanocytic lineage. MELOE-1 contains numerous class II epitopes and one HLA-A*0201-restricted CD8 epitope eliciting a frequent repertoire of high avidity T cells. They designed various synthetic long peptide (SLPs) comprising a CD4 epitope coupled to the CD8 epitope by a serie of linkers of 4 to 6 aa and studied the efficacy of T cell clone activation by SLP-loaded DC in vitro. Particularly, they evaluated the ability of a few selected SLPs to stimulate specific T cells proliferation of PBL from healthy donors in vitro and finally, they explored the vaccination potential of their best SLP candidate in vivo in an HLA*A0201 / HLA-DRB0101 transgenic mouse. Thus, the present invention relates a SLP comprising a CD4 class II peptide linked to a CD8 class I peptide by a specific linker and its use in the treatment of disease like cancers.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a specific linker and a synthetic long peptide (SLP) comprising a CD4 class II peptide linked to a CD8 class I peptide by the specific linker. Particularly, the invention relates to the use of the SLP in the treatment of cancers, infectious diseases, inflammatory diseases or auto-immune diseases in a patient in need thereof.BACKGROUND OF THE INVENTION[0002]It is now established that cancer vaccines triggering T cell activation against tumor antigens can be beneficial to cancer patients (1) although many improvements in the vaccination strategies are still necessary to achieve long-term survival of patients. (2). Various immunogens have been tested, ranging from minimal CTL epitope to the full length recombinant protein. Minimal CTL epitope, usually 9-10 amino acids in length led to limited induction of effector T cells associated with disappointing clinical efficacy. This was likely due to the generation of anergic CD8 T c...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/00C07K14/73C07K14/705A61K47/65
CPCA61K39/0011C07K14/70514A61K2039/876A61K47/65A61K2039/55516C07K14/70517A61K39/00119A61K39/001191A61K39/385A61K2039/62A61K2039/70A61P35/00
Inventor LANG, FRANÇOISRABU, CATHERINE
Owner INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)
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